Abstract 18P
Background
Central nervous system (CNS) metastases are common and life-threatening complications in non-small cell lung cancer (NSCLC) patients with EGFR mutations treated with EGFR-TKIs. At the 2022 ASCO annual meeting, the analysis of phase III AENEAS study showed that aumolertinib, a novel third-generation EGFR-TKI, significantly improved median CNS PFS(CNS mPFS) compared to gefitinib in treatment-naive EGFR-mutant NSCLC patients with CNS metastases (29.0 vs 8.3months, hazard ratios: 0.319). However, for patients without baseline CNS metastasis, data regarding the incidence of symptomatic CNS metastasis with aumolertinib treatment and its risk factors are still rare.
Methods
All consecutive first-line aumolertinib-treated EGFR-mutant advanced NSCLC patients without baseline CNS metastasis after drug registration (April 2020 to February 2023) were included. The cumulative incidence of subsequent symptomatic CNS metastases, CNS mPFS, and their risk factors were estimated using the Kaplan–Meier method and the log-rank test.
Results
Data were retrieved from 63 patients who all received aumolertinib monotherapy as first-line treatment. The median follow-up was 27.4 months. There were 10 pts who developed symptomatic CNS metastases. The CNS mPFS was not reached, with the 12, 18, and 24-month CNS mPFS rate being 100%, 96.3%, and 93.6%, respectively. The cumulative incidence of symptomatic CNS metastasis at 12, 18, and 24 months were 0%, 3.7%, and 6.4 %, respectively. The cumulative incidence with aumolertinib was lower than historical data from first-generation EGFR-TKIs as first-line treatment(2.8-13.9% at 12 months; 9.3-34.6% at 24 months). Moreover, aumolertinib showed equivalent advantages in delaying symptomatic CNS metastasis in patients with L858R and 19del mutations (p=0.9345). Patients with concurrent TP53 mutations, especially mutations in exons 5 or 8, exhibited a higher risk of developing CNS metastasis than those without TP53 mutations or with an unknown status (p=0.0324).
Conclusions
This is the first study to suggest that aumolertinib can reduce the risk of CNS metastasis and prolong CNS disease control in untreated NSCLC patients without baseline CNS metastasis better than first-generation TKIs.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.